Page Three 
September 13, 1978 
The fact that virulent strains of Pneumococcus have 
acquired penicillin resistance in nature hardly justifies 
allowing similar experiments to be performed in the laboratory, 
with or without recombinants. 
If NIH expects to grant exceptions to the 10 liter 
culture limit, particularly for industrial applications, 
it should address now the conditions under which such 
exceptions will be granted and the type of safety requirements 
to be imposed. The containment problems connected with the 
use of large volume fermenters or continuous flow centrifuges 
are qualitatively and quantitatively different from standard 
laboratory equipment. While it is perhaps considered to be 
a problem which will not arise because private industry is 
not technically within the scope of the Guidelines, it would 
be of value if large scale containment were considered both 
to put NIH on record as being concerned about industrial 
problems and to make it more difficult for industry to ignore 
the Guidelines on the grounds that their special problems 
have not been addressed by NIH. NIH should remain as the 
primary source of technical expertise on the safety of 
recombinant DNA activities for both the public and private 
sectors. Further, if legislation is passed, it will be necessary 
that parts II and II of the Guidelines deal with the safety 
of large scale and production processes as well as research 
laboratory procedures. 
My concern with the section on exemptions is that the 
regulatory standard of "no significant risk" is not applied 
to all exemptions. In drafting legislation designed to ensure 
public and environmental safety, this was considered to be 
the only rational grounds upon which total exemptions should 
be based. It is possible to argue convincingly that the 
criteria of I -E-l, I - E -2 , and I -E-3, do indeed satisfy 
this criterion (except for the obvious cases where the host 
cell or vector may already be a dangerous pathogen and would 
be treated accordingly). I am, however, concerned by both 
the lack of precision of the terminology in I - E-4 ("exchange 
DNA by known physiological processes") and by the fact that 
no safety standard is applied. Clearly, there are many 
cases where it could be effectively argued that recombinants 
between natural exchangers do indeed pose no significant 
risk. But, in the general case, this is not a universal truth. 
Specifically what is meant by "known"? Does this mean that 
any exchange event observed once under forced laboratory 
conditions is, therefore, "known", entitling recombinants 
made from the appropriate sources to be exempted from the 
Guidelines? Or does the term imply "nautral"? That is 
must the event be something which occurs readily in nature? 
[A-130] 
